Journal Article

DZNE-2025-01297

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Synphilin-1 modulates alpha-synuclein assembly, release and uptake.

Lázaro, D. F. ; Amen, T. ; Gerhardt, E. ; Song, C. ; Burns, R. ; Kruse, N.DZNE* ; Santos, P. I. ; Milovanovic, D.DZNE* ; Höglinger, G.DZNE* ; Mollenhauer, B.DZNE* ; Luk, K. C. ; Lee, V. M. ; Outeiro, T. F.DZNE*

2025
Springer Nature [London]

This record in other databases:    

Please use a persistent id in citations: doi:10.1038/s41531-025-01144-3

Abstract: Alpha-synuclein (aSyn) is an intrinsically disordered protein involved in phase separation and several age-associated neurodegenerative disorders, including Parkinson's disease. However, its function and pathological role remain elusive. Here, we modeled different aSyn assemblies in living cells by exploiting its interaction with synphilin-1 (Sph1). We developed a model that reports on gel- and solid-like inclusions through coexpression of aSyn and Sph1. Distinct morphological differences emerged between VN-aSyn + aSyn-VC and VN-Sph1 + aSyn-VC assemblies, showing unique antibody recognition, proteinase K resistance, and protein mobilities. The VN-Sph1 + aSyn-VC interaction could be manipulated to alter inclusion size and number. These inclusions also contained lysosomes and AP-1 vesicles, aligning with observations in human brain tissue. Our study offers new insight into aSyn aggregation and release, highlighting the importance of Sph1 and other aSyn-interacting proteins in synucleinopathies, which involve diverse copathologies only now beginning to be understood.

---

Contributing Institute(s):

1. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)
2. Molecular Neuroscience (AG Milovanovic (Berlin))
3. Clinical Research (Munich) (Clinical Research (Munich))

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 351 - Brain Function (POF4-351) (POF4-351)
3. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

---

Database coverage:
; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---